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Biomedical subjects

I M Evans

Publications and source records attributed to I M Evans.

At least 37 records · Page 2Linked to original sources

Perturbation of thyroid hormone homeostasis in the adult and brain function.

Although a critical role of thyroid hormones in mammalian brain development is well established and extensively documented, the adult CNS is often thought to be a thyroid hormone-insensitive organ. The presence in the adult brain of thyroid hormone, along with high levels of nuclear T3 receptors and the strict regulation of intracerebral T3 levels, coupled with overt psychomotor and cognitive dysfunctions in adult-onset dysthyroidism, casts doubt upon this assumption. We have therefore investigated the influence of thyroid hormones on the biochemistry, metabolism and molecular biology of adult rat brain regions and confluent neurons and astrocytes in culture. Our results and those in the literature show that brain nuclear T3 receptor and angiotensinogen mRNA levels and 5'D-II activity are dependent upon normal thyroid hormone concentrations. Several subfractions of cell signalling proteins (G protein alpha subunits) are compromised in hypo- and hyperthyroidism and the activities of protein kinases A and C are up-regulated in the hypothyroid state in a brain region-specific manner. The activities of acid phosphatase and aryl sulphatase A are compromised in the brain of hypothyroid rats, indicating a degree of lysosomal dysfunction, and several neurotransmitter metabolic enzymes and receptor systems are also affected. Metabolic experiments indicate that glutamate and acetate metabolism are compromised in the hypothyroid state, although glucose metabolism remains normal. Primary cultures of confluent neurons and astrocytes also strongly indicate a critical role for thyroid hormones in the control of amino acid uptake, protein synthesis, glycoprotein synthesis and 2-deoxyglucose uptake, in a cell-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multi-dimensional child behavior therapy in the treatment of medically-related anxiety: a practical illustration.

This paper provides a practical illustration of a four-component model for conducting child behavior therapy. It describes the treatment of a 7-year-old boy, whose fears and anxieties regarding impending surgery were interfering with his sleep, concentration, and academic performance. Such childhood difficulties are encountered in primary care medical settings and it is likely that mental health practitioners will be increasingly called upon to treat them. The model provides a framework for selecting, organizing, and implementing strategies based on behavioral principles, with the goal of: (a) reducing the probability of the behavior by ecological change; (b) manipulating the immediate consequences of the problem behavior; (c) facilitating acquisition of new, more adaptive behaviors; and (d) long-term prevention by remedying fundamental deficits. The strategies used for each goal and the success of the overall intervention are described.

Anxiety Disorders↗

Expression of a Brassica napus extensin gene in the vascular system of transgenic tobacco and rape plants.

The organs and tissues where the Brassica napus extA extensin gene is expressed have been identified. The extA gene with 3.75 kb of 5' flanking sequence was transferred to tobacco via disarmed Agrobacterium tumefaciens vectors and transgenic plants regenerated. The gene was found to be inactive in transgenic tobacco leaf, but was active as measured by RNA transcript assays in both stem and root tissues. To determine the cell-specific expression pattern of the extA gene, a promoter-reporter gene fusion construct was made consisting of 1.0 kb of 5' extA sequence fused to the coding region of the glucuronidase (GUS) gene. This fusion construct was introduced into B. napus via Agrobacterium rhizogenes, and expression of GUS in transgenic rape hairy roots was examined. GUS activity was only seen in the vascular tissues of the rape root, and was found to be specifically localised in the phloem.

Agrobacterium tumefaciens↗

A meta-analysis of intervention research with problem behavior: treatment validity and standards of practice.

Published intervention research to remediate problem behavior provides a major source of empirical evidence regarding standards of practice and the relative effectiveness of intervention strategies. A meta-analysis of the developmental disabilities literature for the years 1976 through 1987 was performed. Two measures of intervention effectiveness were employed to evaluate the relations between standards of practice, intervention and participant characteristics, and the treatment validity of different levels of intervention for a range of excess behaviors. The results largely failed to support several widespread assumptions regarding precepts of clinical practice. Suggestions were made concerning clinical-experimental research and publication practices to ensure that future work will provide a more conclusive base.

Adult↗

A gene from pea (Pisum sativum L.) with homology to metallothionein genes.

While searching for 'organ-specific' genes in pea (Pisum sativum L.) we have isolated a gene (designated PsMTA) which has an ORF encoding a predicted protein with some similarity to metallothioneins (MTs). The PsMTA transcript is abundant in roots which have not been exposed to elevated concentrations of trace metals.

Amino Acid Sequence↗

The extensin gene family in oilseed rape (Brassica napus L.): characterisation of sequences of representative members of the family.

A family of cross-hybridising cDNA clones has been isolated from a cDNA library produced with poly(A)+ RNA from the roots of oilseed-rape (Brassica napus L.). The clones were selected as abundantly expressed in root by differential screening of the root cDNA library with cDNA probes prepared from root, green leaf, etiolated leaf and developing seed. mRNA species corresponding to the selected abundant clones were expressed in roots at levels of at least 400 times those in other organs, as shown by Northern blot analysis and RNase protection assays. Complete nucleotide sequence determination of the cDNA clones showed that they encoded proteins homologous to carrot extensin and were the products of at least three different genes. An extensin gene, designated extA, was obtained from an oilseed rape (B. napus L.) genomic library screened with a cDNA species encoding a protein expressed abundantly in roots. The gene is a member of a multigene family, consisting of about 3 members per haploid genome with strong homology to the probe, and a further 20 or so members with weaker homology. The isolated gene, although not identical to the cDNA probe, was also found to be specifically expressed in roots, and was transcribed into a mRNA species approximately 1,300 nucleotides in size. A single transcription start was identified by S1 mapping. The complete nucleotide sequence of the extA gene and its flanking regions has been determined and shown to encode a protein homologous to carrot and tomato extensins.

Amino Acid Sequence↗

Matching treatments to client problems not diagnostic labels: a case for paradigmatic behavior therapy.

The present article critically analyzes the current approach to treatment outcome research and the uncritical use of treatment packages. Comparing various combinations of treatments with groups of clients randomly assigned to these conditions has led to the neglect of individual differences between persons falling into broad diagnostic categories. The inconclusive results of such studies say little about the efficacy of a particular treatment for an individual client and are also not very useful in helping clinicians to decide which specific treatment to use for a given client. Although treatment packages may be attractive and at times helpful to clinicians, their simplistic use is antithetical to the original and unique approach of behavior therapy and no substitute for treatment individualization. Using the example of agoraphobic problems we show how a conceptual understanding of the processes involved in a given clinical problem and the development of an integrative paradigmatic behavioral model may guide the researcher/clinician toward more effective treatment planning. Conceptually derived treatments can be individualized more easily and therefore take better account of individual differences between clients suffering from a seemingly similar problem. Treatment outcome studies should specifically compare the efficacy of matching particular types and constellations of dysfunctional processes with different procedures which specifically target those dysfunctions.

Agoraphobia↗

Effects of part versus whole instructional strategies on skill acquisition and excess behavior.

The relative effectiveness of part versus whole teaching strategies for students with moderate and severe handicaps was investigated. Students were taught two functional tasks using the two methods, with outcome assessed by measures of acquisition, initiation, problem solving, and inappropriate behavior. Although trends in the data suggest the superiority of the part method for acquisition by students with the more severe handicaps, these effects were not significant. The whole method had a significant carryover effect on task preparation and termination. A significant effect of method was found for excess behavior: students taught by the part method exhibited less excess behavior than did students taught by the whole method.

Achievement↗

Regulation of storage-protein synthesis in pea (Pisum sativum L.) cotyledons under conditions of sulphur deficiency.

The effects of sulphur deficiency on the expression of storage-protein genes in developing pea (Pisum sativum) cotyledons were studied. Legumin-gene transcription was decreased by S-deficiency, but not to the same extent as the decrease in the level of legumin mRNA. Vicilin-gene transcription was not significantly affected. Control of gene expression may thus occur during transcription and/or post-transcriptional events.

Cell Nucleus↗

Control of storage-protein synthesis during seed development in pea (Pisum sativum L.).

The tissue-specific syntheses of seed storage proteins in the cotyledons of developing pea (Pisum sativum L.) seeds have been demonstrated by estimates of their qualitative and quantitative accumulation by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and rocket immunoelectrophoresis respectively. Vicilin-fraction proteins initially accumulated faster than legumin, but whereas legumin was accumulated throughout development, different components of the vicilin fraction had their predominant periods of synthesis at different stages of development. The translation products in vitro of polysomes isolated from cotyledons at different stages of development reflected the synthesis in vivo of storage-protein polypeptides at corresponding times. The levels of storage-protein mRNA species during development were estimated by 'Northern' hybridization using cloned complementary-DNA probes. This technique showed that the levels of legumin and vicilin (47000-Mr precursors) mRNA species increased and decreased in agreement with estimated rates of synthesis of the respective polypeptides. The relative amounts of these messages, estimated by kinetic hybridization were also consistent. Legumin mRNA was present in leaf poly(A)+ RNA at less than one-thousandth of the level in cotyledon poly(A)+ (polyadenylated) RNA, demonstrating tissue-specific expression. Evidence is presented that storage-protein mRNA species are relatively long-lived, and it is suggested that storage-protein synthesis is regulated primarily at the transcriptional level.

DNA↗

Long-term measurement of skeletal and lean body mass in Paget's disease of bone treated with synthetic human calcitonin.

Total body calcium (an index of skeletal mass), ulnar bone density, and total body potassium (lean body mass) were followed for up to 5 years in 38 patients with Paget's disease during treatment with synthetic human calcitonin. Calcium was measured by neutron activation, ulnar density by X-ray photodensitometry, and potassium by counting its natural 40K radioactivity. There was a significant rise in total skeletal mass in a group of 8 patients in the 12 months following the start of therapy, but overall, total bone mass and ulnar density remained constant during treatment. Small mean losses of body potassium were observed (approximately 4%) after several years elapsed on treatment. Over an average period of 12 months after discontinuation of therapy in 21 patients there was no significant mean change in calcium or potassium. The means of the ratios of total body calcium divided by predicted normal calcium (over the whole period of measurement) were 1.08 (males) and 0.99 (females) and were not significantly different. Comparison of the ulnar densities of patients and normal subjects gave similar results. The average ratio of measured to predicted normal potassium was 1.13 (both males and females). Thus there was no indication of depletion in skeletal mass below normal either in the untreated disease or resulting from treatment.

Absorptiometry, Photon↗

Pharmacology and therapeutic use of calcitonin.

Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. A major physiological function of the hormone appears to be the protection of the skeleton against resorption in humans. It thus opposes the resorptive actions of parathyroid hormone and 1,25 dihydroxyvitamin D. This action is utilised pharmacologically in order to treat diseases where increased bone resorption is a major component. The efficacy of calcitonin in the treatment of Paget's disease of bone is well established, especially as it is currently the most effective agent in the treatment of the osteolytic form of the disease. In other bone diseases where resorption of bone is a component it is likely to be worthy of a trial of therapy. There are also sound theoretical reasons why calcitonin may be of benefit in the treatment of certain osteoporoses, especially in combination with other agents. Most recent studies would seem to support his view. A disadvantage of calcitonin therapy is that the hormone has to be administered parenterally, although future developments may obviate this. It is, however, a form of retreatment which is free of any long term serious side effects, and calcitonin now has a definite place in the management of specific bone and calcium disorders.

Animals↗

Synthesis of complementary DNAs to partially purified mRNAs coding for the storage proteins of Pisum sativum (L).

mRNAs in developing cotyledons of Pisum sativum (L) coding for the major storage proteins, vicilin and legumin, were partially purified and characterized. Both vicilin (47 000 and 50 000 daltons) and legumin (60 000) precursor subunits were translated in the reticulocyte lysate cell-free system when driven by 18 S poly(A)+-RNA. Total poly(A)+-RNA, purified twice by oligo(dT)-cellulose chromatography, migrated on dissociating gels on electrophoresis as a polydisperse peak with three maxima at 18, 14 and 12 S. This mRNA preparation was used as a template for the synthesis of single- and double-stranded cDNAs under optimized reaction conditions. Analysis of single-stranded cDNA on dissociating gels showed a polydisperse profile, with three major components of molecular weights 3.7 x 10(5), 2.3 X 10(5) and 2.0 X 10(5). The double-stranded cDNA preparation contained some contaminating single strands, some partially double-stranded molecules formed by continuation of looped first strands, and some molecules which were primarily single strands protected by partial second strands. Restriction endonucleases cut the double-stranded cDNA preparation into several discrete fragments.

Base Composition↗